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blood brain barrier ischemia

Yu-Huan Cui, Xiao-Qing Zhang, Nai-Dong Wang, Mao-Dong Zheng, Juan Yan
Brain endothelial permeability plays a crucial role in blood-brain barrier (BBB), but the permeability enhancement in cerebral ischemia reperfusion (I/R). Vitexin has certain neuroprotective effects, but the effect brain endothelial permeability in I/R injury was unknown. In this study, the effects of Vitexin on endothelial permeability and the underlying mechanisms in human brain microvascular endothelial cells (HBMEc) I/R injury model were investigated. Cell viability, lactate dehydrogenase (LDH), inflammation and apoptosis were detected...
March 12, 2019: European Journal of Pharmacology
Kelly M DeMars, Changjun Yang, Eduardo Candelario-Jalil
Neuroinflammation after stroke significantly contributes to neuronal cell death. Bromodomain and Extra Terminal Domain (BET) proteins are essential to inflammatory gene transcription. BET proteins (BRD2, BRD3, BRD4, and BRDT) have varied effects including chromatin remodeling, histone acetyltransferase activity, and as scaffolds to recruit transcription factors; they couple chromatin remodeling with transcription. BRD2/4 are of particularly interest to stroke-induced neuroinflammation that contributes to delayed cell death as they are required for NF-κB-dependent gene transcription...
March 11, 2019: Neurochemistry International
Shu Yang, Hong Jin, Zhi-Gang Zhao
Tight junctions (TJs) serve an important role in maintaining the integrity of the blood-brain barrier (BBB), while neurological disorders, including ischemic stroke, induce TJ disruption and increase BBB permeability; results include edema formation and hemorrhage transformation. Cerebral endothelium protection presents a promising approach in ischemic stroke therapy. In the current study, protective effects of the epidermal growth factor (EGF) on ischemia-induced disruption of BBB integrity were examined using an oxygen-glucose deprivation (OGD) model in bEnd3 cells...
March 2019: Experimental and Therapeutic Medicine
Sipeng Wu, Ning Wang, Jing Li, Guangyun Wang, Sai Wang Seto, Dennis Chang, Huazheng Liang
Abstract Chuanxiong rhizome has been widely used for the treatment of cerebral vascular disease in traditional Chinese medicine. The integrity of blood-brain barrier (BBB) is closely linked to the cerebral vascular disease. The protective effects of ligustilide, the major bioactive component in Chuanxiong rhizome, on cerebral blood vessel has been reported previously, but its effects and potential mechanism on BBB has not been entirely clarified. In the current work, the effects of ligustilide on BBB permeability and the underlying molecular mechanisms had been investigated using the model of BBB established by co-culturing astrocytes and brain microvascular endothelial cells isolated from the rat brain...
March 6, 2019: Journal of Cardiovascular Pharmacology
Guodong Xu, Chun Li, Anne L Parsiola, Jiyu Li, Kimberly D McCarter, Runhua Shi, William G Mayhan, Hong Sun
Chronic ethanol consumption dose-dependently affects both incidence and prognosis of ischemic stroke. Our goal was to determine whether the influence of chronic ethanol consumption on ischemic stroke is related to an altered inflammatory profile in the brain. Male C57BL/6J mice were divided into six groups and gavage fed with 0.175, 0.35, 0.7, 1.4, 2.8 g/kg/day ethanol or volume-matched water once a day for 8 weeks. Adhesion molecules, microglial activation, neutrophil infiltration, pro- and anti-inflammatory cytokines/chemokines, blood-brain barrier (BBB) permeability, and matrix metallopeptidases (MMPs) in the cerebral cortex before and following a 90-min unilateral middle cerebral artery occlusion (MCAO)/24-h reperfusion were evaluated...
2019: Frontiers in Cellular Neuroscience
Dong You, Hong You
OBJECTIVE: This study was performed to investigate effect of long non-coding RNA (lncRNA) MEG3 on nerve growth and neurological impairment in a rat model after cerebral ischemia-reperfusion injury (IRI) through the Wnt/β-catenin signaling pathway. METHODS: Rat models of middle cerebral artery occlusion (MCAO) were established to stimulate an environment of cerebral IRI. The modeled rats were subjected to negative control (NC), MEG3, si-MEG3, classical Wnt pathway inhibitor DKK1 or classical Wnt pathway activator LiCl to validate the effect of MEG3 on neurological impairment and nerve growth...
March 2019: Biomedicine & Pharmacotherapy
Huangcheng Song, Shuai Yuan, Zhuwei Zhang, Juyi Zhang, Peng Zhang, Jie Cao, Haiying Li, Xiang Li, Haitao Shen, Zhong Wang, Gang Chen
Sodium/hydrogen exchanger 1 (NHE1) plays an essential role in maintaining intracellular pH (pHi) homeostasis in the central nervous system (CNS) under physiological conditions, and it is also associated with neuronal death and intracellular Na+ and Ca2+ overload induced by cerebral ischemia. However, its roles and underlying mechanisms in early brain injury (EBI) induced by subarachnoid hemorrhage (SAH) have not been fully explored. In this research, a SAH model in adult male rat was established through injecting autologous arterial blood into prechiasmatic cistern...
March 6, 2019: Cell Transplantation
Núria DeGregorio-Rocasolano, Octavi Martí-Sistac, Teresa Gasull
In general, iron represents a double-edged sword in metabolism in most tissues, especially in the brain. Although the high metabolic demands of brain cells require iron as a redox-active metal for ATP-producing enzymes, the brain is highly vulnerable to the devastating consequences of excessive iron-induced oxidative stress and, as recently found, to ferroptosis as well. The blood-brain barrier (BBB) protects the brain from fluctuations in systemic iron. Under pathological conditions, especially in acute brain pathologies such as stroke, the BBB is disrupted, and iron pools from the blood gain sudden access to the brain parenchyma, which is crucial in mediating stroke-induced neurodegeneration...
2019: Frontiers in Neuroscience
Fenghua Chen, Zhongfang Weng, Qinghai Xia, Catherine Cao, Rehana K Leak, Lihong Han, Jian Xiao, Steven H Graham, Guodong Cao
Our previous study indicated that nicotinamide phosphoribosyltransferase (NAMPT) is released from cells and might be an important extracellular neuroprotective factor in brain ischemia. Here, we tested whether NAMPT protects against ischemic brain injury when administered directly into the intracerebroventricular (ICV) compartment of the cranium. Recombinant NAMPT protein (2 μg) was delivered ICV in mice subjected to 45-min middle cerebral artery occlusion (MCAO), and the effects on infarct volume, sensorimotor function, microglia/macrophage polarization, neutrophil infiltration, and BBB integrity were analyzed...
February 28, 2019: Translational Stroke Research
Rebecca Ward, Weiguo Li, Yasir Abdul, LaDonya Jackson, Guangkuo Dong, Sarah Jamil, Jessica Filosa, Susan C Fagan, Adviye Ergul
Diabetes increases the risk and worsens the progression of cognitive impairment via the greater occurrence of small vessel disease and stroke. Yet, the underlying mechanisms are not fully understood. It is now accepted that cardiovascular health is critical for brain health and any neurorestorative approaches to prevent/delay cognitive deficits should target the conceptual neurovascular unit (NVU) rather than neurons alone. We have recently shown that there is augmented hippocampal NVU remodeling after a remote ischemic injury in diabetes...
February 25, 2019: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Wei-Yuan Huang, Gang Wu, Shan-Xi Guo, Dao-Ying Geng, Jian-Jun Li, Kai Yang
The aim of the study is to verify the effect of hyperglycemia on ischemia-reperfusion injury and to explore the feasibility of noninvasive observation of ischemic-reperfusion injury in hyperglycemic ischemic stroke by MRI technique. According to the duration of ischemia and blood glucose levels, 40 rats were divided into hyperglycemic ischemic 2-hr (H-I2h), hyperglycemic ischemic 6-hr (H-I6h), non- hyperglycemic ischemic 2-hr (NH-I2h), and non- hyperglycemic ischemic 6-hr (NH-I6h) groups. T2W imaging, DW imaging, T2 mapping, T2* mapping, DCE, and T1 mapping after enhancement sequences were acquired before reperfusion and approximately 3-hr after reperfusion...
February 27, 2019: Scientific Reports
Hideki Kanamaru, Hidenori Suzuki
Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities. Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure, followed by global cerebral ischemia. Post-subarachnoid hemorrhage ischemia, tissue injuries as well as extravasated blood components and the breakdown products activate microglia, astrocytes and Toll-like receptor 4, and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades...
July 2019: Neural Regeneration Research
Sathyasivam Kaviarasi, Eiji Yuba, Atsushi Harada, Uma Maheswari Krishnan
Cerebral ischemia is a deadly condition that arises due to blockage of the blood vessels in the brain leading to oxygen deficiency thereby arresting brain functions and resulting in death or permanent impairment. Though a myriad of factors has been proposed to cause cerebral ischemia, it has been generally regarded as an old age-associated malady. However, unhealthy diet, stressful lifestyle and deteriorating environment quality has dramatically reduced the age on onset as well as the number of victims in recent years...
February 22, 2019: Journal of Controlled Release: Official Journal of the Controlled Release Society
Conor O'Boyle, Michael J Haley, Eloise Lemarchand, Craig J Smith, Stuart M Allan, Joanne E Konkel, Catherine B Lawrence
BACKGROUND: Stroke is a major cause of disability and mortality. Poorer outcome after stroke is associated with concomitant inflammatory and infectious disease. Periodontitis is a chronic inflammatory disease of the dental supporting structures and is a prominent risk factor for many systemic disorders, including cardiovascular disease and stroke. While epidemiological studies suggest that periodontitis increases the likelihood of stroke, its impact on stroke severity is poorly understood...
February 22, 2019: International Journal of Stroke: Official Journal of the International Stroke Society
N R Bonetti, C Diaz-Cañestro, L Liberale, M Crucet, A Akhmedov, M Merlini, M F Reiner, S Gobbato, S Stivala, G Kollias, F Ruschitzka, T F Lüscher, J H Beer, G G Camici
Rheumatoid Arthritis (RA) is a chronic inflammatory disorder where incidence and severity of myocardial infarction are increased. Data on the incidence and outcome of stroke are conflicting. Thus, we investigated outcome after Ischemia/Reperfusion (I/R) brain injury in a mouse model of RA and assessed for the role of the tumour necrosis factor-α (TNF-α) inhibitor Infliximab herein. We used a TNF-α reliant mouse model of RA. RA and wildtype (WT) animals were treated with vehicle (RA/WT) or Infliximab (RA Infliximab) for 4 weeks, before undergoing I/R brain injury...
February 18, 2019: Scientific Reports
Abhijit Nirwane, Jessica Johnson, Benjamin Nguyen, Jeffrey H Miner, Yao Yao
At the blood-brain barrier (BBB), laminin-α5 is predominantly synthesized by endothelial cells and mural cells. Endothelial laminin-α5 is dispensable for BBB maintenance under homeostatic conditions but inhibits inflammatory cell extravasation in pathological conditions. Whether mural cell-derived laminin-α5 is involved in vascular integrity regulation, however, remains unknown. To answer this question, we generated transgenic mice with laminin-α5 deficiency in mural cells (α5-PKO). Under homeostatic conditions, no defects in BBB integrity and cerebral blood flow (CBF) were observed in α5-PKO mice, suggesting that mural cell-derived laminin-α5 is dispensable for BBB maintenance and CBF regulation under homeostatic conditions...
February 18, 2019: Acta Neuropathologica Communications
Martin Krueger, Bianca Mages, Constance Hobusch, Dominik Michalski
In the setting of stroke, ischemia-related blood-brain barrier (BBB) dysfunction aggravates the cerebral edema, which critically impacts on the clinical outcome. Further, an impaired vascular integrity is associated with the risk of intracranial bleeding, especially after therapeutic recanalization. Therefore, the present study was aimed to investigate early vascular alterations from 30 min to 4 h after experimental middle cerebral artery occlusion (MCAO) in mice. Here, an extravasation of the permeability marker FITC-albumin was detectable in animals 2 and 4 h after MCAO...
February 11, 2019: Acta Neuropathologica Communications
Shi-Peng Li, Li-Gong Bian, Xi-Yue Fu, Qing-Long Ai, Yue Sui, Ai-Dan Zhang, Hui-Qing Gao, Lian-Mei Zhong, Di Lu
Brain damage, including blood-brain barrier (BBB) dysfunction, neurological behavior deficit, cerebral infarction and inflammation, is commonly caused by ischemic-reperfusion (I/R) injury. Prevention of the above biological process defects is considered beneficial for patient recovery after I/R injury. This study was aimed to assess the neuroprotective effect of Gastrodin (GAS), an herbal agent, in experimentally induced cerebral ischemia. Sprague-Dawley adult rats were randomly divided into six groups: Sham-operated control group (Sham), middle cerebral artery occlusion (MCAO) group, GAS (50, 100, and 200 mg/kg) pretreatment + MCAO groups (GAS) and Nimodipine (NIM) + MCAO, namely, the NIM group...
February 8, 2019: Brain Research
Philipp Berndt, Lars Winkler, Jimmi Cording, Olga Breitkreuz-Korff, André Rex, Sophie Dithmer, Valentina Rausch, Rosel Blasig, Matthias Richter, Anje Sporbert, Hartwig Wolburg, Ingolf E Blasig, Reiner F Haseloff
At the blood-brain barrier (BBB), claudin (Cldn)-5 is thought to be the dominant tight junction (TJ) protein, with minor contributions from Cldn3 and -12, and occludin. However, the BBB appears ultrastructurally normal in Cldn5 knock-out mice, suggesting that further Cldns and/or TJ-associated marvel proteins (TAMPs) are involved. Microdissected human and murine brain capillaries, quickly frozen to recapitulate the in vivo situation, showed high transcript expression of Cldn5, -11, -12, and -25, and occludin, but also abundant levels of Cldn1 and -27 in man...
February 7, 2019: Cellular and Molecular Life Sciences: CMLS
Audrey P Fan, Ahmed A Khalil, Jochen B Fiebach, Greg Zaharchuk, Arno Villringer, Kersten Villringer, Claudine J Gauthier
Recent clinical trials of new revascularization therapies in acute ischemic stroke have highlighted the importance of physiological imaging to identify optimal treatments for patients. Oxygen extraction fraction (OEF) is a hallmark of at-risk tissue in stroke, and can be quantified from the susceptibility effect of deoxyhemoglobin molecules in venous blood on MRI phase scans. We measured OEF within cerebral veins using advanced quantitative susceptibility mapping (QSM) MRI reconstructions in 20 acute stroke patients...
February 7, 2019: Journal of Cerebral Blood Flow and Metabolism
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